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1. Miro-dependent mitochondrial pool of CENP-F and its farnesylated C-terminal domain are dispensable for normal development in mice

Author

Peterka, Martin and Kornmann, Benoît

Subjects
rho GTP-Binding Proteins, Chromosomal Proteins, Non-Histone, Immunofluorescence, Mutant, Mitochondrion, Biochemistry, Chromosome segregation, Mice, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, Eye Abnormalities, Cell Cycle and Cell Division, Energy-Producing Organelles, Connective Tissue Cells, 0303 health sciences, Kinetochore, Microfilament Proteins, Chemical Reactions, Animal Models, Farnesylation, Phenotype, Mitochondria, Cell biology, Chemistry, Experimental Organism Systems, Mice, Inbred DBA, Connective Tissue, Cell Processes, 030220 oncology & carcinogenesis, Physical Sciences, Microcephaly, Cellular Structures and Organelles, Cellular Types, Anatomy, Protein Binding, Research Article, lcsh:QH426-470, Intestinal Atresia, BUB1, Mice, Transgenic, Mouse Models, macromolecular substances, Bioenergetics, Biology, Research and Analysis Methods, Cell Line, Mitochondrial Proteins, 03 medical and health sciences, Model Organisms, Downregulation and upregulation, Genetics, Animals, Humans, Point Mutation, Protein Interaction Domains and Motifs, Amino Acid Sequence, Immunoassays, Molecular Biology Techniques, Molecular Biology, Cytokinesis, 030304 developmental biology, Prenylation, Biology and Life Sciences, Cell Biology, Fibroblasts, Mice, Inbred C57BL, lcsh:Genetics, Biological Tissue, Amino Acid Substitution, Mutation, Animal Studies, Immunologic Techniques, CRISPR-Cas Systems, Cloning
Abstract

CENP-F is a large, microtubule-binding protein that regulates multiple cellular processes including chromosome segregation and mitochondrial trafficking at cytokinesis. This multiplicity of functions is mediated through the binding of various partners, like Bub1 at the kinetochore and Miro at mitochondria. Due to the multifunctionality of CENP-F, the cellular phenotypes observed upon its depletion are difficult to interpret and there is a need to genetically separate its different functions by preventing binding to selected partners. Here we engineer a CENP-F point-mutant that is deficient in Miro binding and thus is unable to localize to mitochondria, but retains other localizations. We introduce this mutation in cultured human cells using CRISPR/Cas9 system and show it causes a defect in mitochondrial spreading similar to that observed upon Miro depletion. We further create a mouse model carrying this CENP-F variant, as well as truncated CENP-F mutants lacking the farnesylated C-terminus of the protein. Importantly, one of these truncations leads to ~80% downregulation of CENP-F expression. We observe that, despite the phenotypes apparent in cultured cells, mutant mice develop normally. Taken together, these mice will serve as important models to study CENP-F biology at organismal level. In addition, because truncations of CENP-F in humans cause a lethal disease termed Strømme syndrome, they might also be relevant disease models., PLoS Genetics, 15 (3), ISSN:1553-7390, ISSN:1553-7404

Published
2019

2. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study

Author

Wachter, Rolf, Senni, Michele, Belohlavek, Jan, Straburzynska‐Migaj, Ewa, Witte, Klaus K., Kobalava, Zhanna, Fonseca, Candida, Goncalvesova, Eva, Cavusoglu, Yuksel, Fernandez, Alberto, Chaaban, Said, Bøhmer, Ellen, Pouleur, Anne‐Catherine, Mueller, Christian, Tribouilloy, Christophe, Lonn, Eva, A.L. Buraiki, Jehad, Gniot, Jacek, Mozheiko, Maria, Lelonek, Malgorzata, Noè, Adele, Schwende, Heike, Bao, Weibin, Butylin, Dmytro, Pascual‐Figal, Domingo, Dominguez, Antonio Reyes, Horacek, Thomas, del Rio, Enrique Garcia, Mueller, Christian Eugen, Straburzynska-Migaj, Ewa, Slanina, Miroslav, vom Dahl, Juergen, Ryding, Alisdair, Moriarty, Andrew, Robles, Manuel Beltran, Villota, Julio Nunez, Quintana, Antonio Garcia, Nitschke, Thorsten, Manuel Garcia Pinilla, Jose, Bonet, Luis Almenar, Filali zaatari, MD, Samia, Spinar, Jindrich, Musial, Wlodzimierz, Abdelbaki, Khaled, Fehske, Wolfgang, Bott, Michael Carlos, Hoegalmen, Geir, Leiro, Marisa Crespo, Ozcan, Ismail Turkay, Mullens, Wilfried, Kryza, Radim, Al-Ani, Riadh, Loboz-Grudzien, Krystyna, Ermoshkina, Lyudmila, Hojerova, Silvia, Fernandez, Alberto Alfredo, Spinarova, Lenka, Lapp, Harald, Bulut, Efraim, Almeida, Filipa, Vishnevsky, Alexander, Belicova, Margita, Pascual, Domingo, Witte, Klaus, Wong, Kenneth, Droogne, Walter, Delforge, Marc, Peterka, Martin, Olbrich, Hans‐Georg, Carugo, Stefano, Nessler, Jadwiga, McGill, Thao Huynh, Huegl, Burkhard, Akin, Ibrahim, Moreira, Ilidio, Baglikov, Andrey, Thambyrajah, Jeetendra, Hayes, Chris, Barrionuevo, Marcelo Raul, Yigit, Zerrin, Kaya, Hakki, Klimsa, Zdenek, Radvan, Martin, Kadel, Christoph, Landmesser, Ulf, Di Tano, Giuseppe, Lisik, Malgorzata Buksinska, Oliveira, Luis, Marques, Irene, Santos, Luis Miguel, Lenner, Egon, Letavay, Peter, Bueno, Manuel Gomez, Mota, Paula, Wong, Aaron, Bailey, Kristian, Foley, Paul, Hasbani, Eduardo, Virani, Sean, Massih, Tony Abdel, Al‐Saif, Shukri, Taborsky, Milos, Kaislerova, Marta, Motovska, Zuzana, Praha, Cohen, Aron Ariel, Logeart, Damien, Endemann, Dierk, Ferreira, Daniel, Brito, Dulce, Kycina, Peter, Bollano, Entela, Basilio, Enrique Galve, Rubio, Lorenzo Facila, Aguado, Marcos Garcia, Schiavi, Lilia Beatriz, Zivano, Daniel Francisco, Sayed, Ali El, Heyse, Alex, Schee, Alexandr, Polasek, Rostislav, Houra, Marek, Seronde, Marie France, Galinier, Michel, Noutsias, Michel, Schwimmbeck, Peter, Voigt, Ingo, Westermann, Dirk, Pulignano, Giovanni, Vegsundvaag, Johnny, Alexandre Da Silva Antunes, Jose, Monteiro, Pedro, Stevlik, Jan, Hulkoova, Beata, Juan Castro Fernandez, Antonio, Davies, Ceri, Squire, Iain, Meyer, Philippe, Sheppard, Richard, Sahin, Tayfun, Sochor, Karel, De Geeter, Guillaume, Schmeisser, Alexander, Weil, Joachim, Soares, Ana Oliveira, Vasilevna, Olga Bulashova, Oshurkov, Andrey, Sunderland, Shahid Junejo, Glover, Jason, Exequiel, Tomas, Decoulx, Eric, Meyer, Sven, Muenzel, Thomas, Frioes, Fernando, Arbolishvili, Georgy, Tokarcikova, Anna, Karlstrom, Patric, Carles Trullas Vila, Joan, Perez, Gonzalo Pena, Sankaranarayanan, Rajiv, Nageh, Thuraia, Alasia, Diego Cristian, Refaat, Marwan, Demirkan, Burcu, Al-Buraiki, Jehad, Karabsheh, Shadi, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Wachter, R, Senni, M, Belohlavek, J, Straburzynska-Migaj, E, Witte, K, Kobalava, Z, Fonseca, C, Goncalvesova, E, Cavusoglu, Y, Fernandez, A, Chaaban, S, Bøhmer, E, Pouleur, A, Mueller, C, Tribouilloy, C, Lonn, E, A L Buraiki, J, Gniot, J, Mozheiko, M, Lelonek, M, Noè, A, Schwende, H, Bao, W, Butylin, D, Pascual-Figal, D, and Transition, I

Subjects
Male, medicine.medical_specialty, Acute decompensated heart failure, Tetrazoles, Heart failure, 030204 cardiovascular system & hematology, Sacubitril, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Hospitalisation, Humans, Sacubitril/valsartan, Aged, Angiotensin receptor–neprilysin inhibitor, Heart Failure, Ejection fraction, Dose-Response Relationship, Drug, business.industry, Aminobutyrates, Biphenyl Compounds, Hemodynamics, medicine.disease, Angiotensin receptor-neprilysin inhibitor, Patient Discharge, 3. Good health, Discontinuation, Drug Combinations, Treatment Outcome, Valsartan, Tolerability, Female, Neprilysin, business, Cardiology and Cardiovascular Medicine, Sacubitril, Valsartan, medicine.drug, Follow-Up Studies
Abstract

AIMS: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). METHODS AND RESULTS: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46). CONCLUSIONS: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02661217. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons peerReviewed

Published
2019

4. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Author

Maggioni, Aldo P., Greene, Stephen J., Fonarow, Gregg C., Böhm, Michael, Zannad, Faiez, Solomon, Scott D., Lewis, Eldrin F., Baschiera, Fabio, Hua, Tsushung A., Gimpelewicz, Claudio R., Lesogor, Anastasia, Gheorghiade, Mihai, Ramos, Silvina, Luna, Alejandra, Miriuka, Santiago, Diez, Mirta, Perna, Eduardo, Luquez, Hugo, Pinna, Jorge Garcia, Castagnino, Jorge, Alvarenga, Pablo, Ibañez, Julio, Blumberg, Eduardo Salmon, Dizeo, Claudio, Guerrero, Rodolfo Ahuad, Schygiel, Pablo, Milesi, Rodolfo, Sosa, Carlos, Hominal, Miguel, Marquez, Lilia Lobo, Poy, Carlos, Hasbani, Eduardo, Vico, Marisa, Fernandez, Alberto, Vita, Nestor, Vanhaecke, Johan, De Keulenaer, Gilles, Striekwold, Harry, Vervoort, Geert, Vrolix, Mathias, Henry, Philippe, Dendale, Paul, Smolders, Walter, Marechal, Patrick, Vandekerckhove, Hans, Oliveira, Mucio, Neuenschwande, Fernando, Reis, Gilmar, Saraiva, Jose, Bodanese, Luiz, Canesin, Manoel, Greco, Oswaldo, Bassan, Roberto, Marino, Roberto Luis, Giannetti, Nadia, Moe, Gordon, Sussex, Bruce, Sheppard, Richard, Huynh, Thao, Stewart, Robert, Haddad, Haissam, Echeverria, Luis, Quintero, Adalberto, Torres, Adriana, Jaramillo, Mónica, Lopez, Mónica, Mendoza, Fernan, Florez, Noel, Cotes, Carlos, Garcia, Magali, Belohlavek, Jan, Hradec, Jaromir, Peterka, Martin, Gregor, Pavel, Monhart, Zdenek, Jansky, Petr, Kettner, Jiri, Reichert, Petr, Spinar, Jindrich, Brabec, Tomas, Hutyra, Martin, Solar, Miroslav, Pietilä, Mikko, Nyman, Kai, Pajari, Risto, Cohen, Ariel, Galinier, Michel, Gosse, Philippe, Livarek, Bernard, Neuder, Yannick, Jourdain, Patrick, Picard, François, Isnard, Richard, Hoppe, Uta, Kaeaeb, Stefan, Rosocha, Stefan, Prondzinsky, Roland, Felix, Stephan, Duengen, Hans-Dirk, Figulla, Hans-Reiner, Fischer, Sven, Behrens, Steffen, Stawowy, Philipp, Kruells-Muench, Juergen, Knebel, Fabian, Nienaber, Christoph, Werner, Dierk, Aron, Wilma, Remppis, Bjoern, Hambrecht, Rainer, Kisters, Klaus, Werner, Nikos, Hoffmann, Stefan, Rossol, Siegbert, Geiss, Ernst, Graf, Kristof, Hamann, Frank, von Scheidt, Wolfgang, Schwinger, Robert, Tebbe, Ulrich, Costard-Jaeckle, Angelika, Lueders, Stephan, Heitzer, Thomas, Leutermann-Oei, Marie-Louise, Braun-Dullaeus, Ruediger, Roehnisch, Jens-Uwe, Muth, Gerhard, Goette, Andreas, Rotter, Achim, Ebelt, Henning, Olbrich, Hans-Georg, Mitrovic, Veselin, Hengstenberg, Christian, Schellong, Sebastian, Zamolyi, Karoly, Vertes, Andras, Matoltsy, Andras, Palinkas, Attila, Herczeg, Bela, Apro, Dezso, Lupkovics, Geza, Tomcsanyi, Janos, Toth, Kalman, Mathur, Atul, Banker, Darshan, Bharani, Anil, Arneja, Jaspal, Khan, Aziz, Gadkari, Milind, Hiremath, Jagdish, Patki, Nitin, Kumbla, Makund, Santosh, M.J., Ravikishore, A.G., Abhaichand, Rajpal, Maniyal, Vijayakukmar, Nanjappa, Manjunath, Reddy, P. Naveen, Chockalingam, Kulasekaran, Premchand, Rajendra, Mahajan, Vijay, Lewis, Basil, Wexler, Dov, Shochat, Michael, Keren, Andre, Omary, Muhamad, Katz, Amos, Marmor, Alon, Lembo, Giuseppe, Di Somma, Salvatore, Boccanelli, Alessandro, Barbiero, Mario, Pajes, Giuseppe, De Servi, Stefano, Greco, Dott Cosimo, De Santis, Fernando, Floresta, Agata, Visconti, Luigi Oltrona, Piovaccari, Giancarlo, Cavallini, Claudio, Di Biase, Matteo, Masini, Dott Franco, Vassanelli, Corrado, Viecca, Maurizio, Cangemi, Dott Francesco, Pirelli, Salvatore, Borghi, Claudio, Volpe, Massimo, Branzi, Angelo, Percoco, Dott Giovanni, Severi, Silvia, Santini, Alberto, De Lorenzi, Ettore, Metra, Marco, Zacà, Valerio, Mortara, Andrea, Tranquilino, Francisco P., Babilonia, Noe A., Ferrolino, Arthur M., Manlutac, Benjamin, Dluzniewski, Miroslaw, Dzielinska, Zofia, Nowalany-Kozie, Ewa, Mazurek, Walentyna, Wierzchowiecki, Jerzy, Wysokinski, Andrzej, Szachniewicz, Joanna, Romanowski, Witold, Krauze-Wielicka, Magdalena, Jankowski, Piotr, Berkowski, Piotr, Szelemej, Roman, Kleinrok, Andrzej, Kornacewicz-Jac, Zdzislawa, Vintila, Marius, Vladoianu, Mircea, Militaru, Constantin, Dan, Gheorghe, Dorobantu, Maria, Dragulescu, Stefan, Kostenko, Victor, Vishnevsky, Alexandr, Goloschekin, Boris, Tyrenko, Vadim, Gordienko, Alexander, Kislyak, Oxana, Martsevich, Sergey, Kuchmin, Alexey, Karpov, Yurii, Fomin, Igor, Shvarts, Yury, Orlikova, Olga, Ershova, Olga, Berkovich, Olga, Sitnikova, Maria, Pakhomova, Inna, Boldueva, Svetlana, Tyurina, Tatiana, Simanenkov, Vladimir, Boyarkin, Mikhail, Novikova, Nina, Tereschenko, Sergey, Zadionchenko, Vladimir, Shogenov, Zaur, Gordeev, Ivan, Moiseev, Valentin, Wong, Raymond, Ong, Hean Yee, Le Tan, Ju, Goncalvesova, Eva, Kovar, Frantisek, Skalina, Ivan, Kasperova, Viera, Hojerova, Silvia, Szentivanyi, Miroslav, Stancak, Branislav, Babcak, Marian, Kycina, Peter, Poliacik, Pavol, Toth, Peter, Sirotiakova, Jana, de Sa, Esteban Lopez, Bueno, Manuel Gomez, Selles, Manuel Martinez, Cabrera, Jose Angel, Freire, Ramon Bover, Gonzalez Juanatey, Jose Ramon, Comin, Josep, Soriano, FranciscoRidocci, Lopez, Alejandro, Vicho, Raul, Lama, Manuel Geraldia, Schaufelberger, Maria, Brunotte, Richard, Ullman, Bengt, Hagerman, Inger, Cizinsky, Stella, Cherng, Wen-Jin, Yu, Wen-Chung, Kuo, Chi-Tai, Chang, Kuan-Cheng, Lai, Wen-Ter, Kuo, Jen-Yuan, Ural, Dilek, Badak, Ozer, Akin, Mustafa, Yigit, Zerrin, Yokusoglu, Mehmet, Yilmaz, Mehmet, Abaci, Adnan, Ebinc, Haksun, Perlman, Richard, Parish, David, Bergin, James, Burnham, Kenneth, Brown, Christopher, Lundbye, Justin, Williams, Celeste, Eisen, Howard, Juneman, Elizabeth, Joseph, Susan, Peberdy, Mary Ann, Peura, Jennifer, Gupta, Vishal, Habet, Kalim, French, William, Mody, Freny, Graham, Susan, Hazelrigg, Monica, Chung, Eugene, Dunlap, Stephanie, Nikolaidis, Lazaros, Najjar, Samer, Katz, Richard, Murali, Srinivas, Izzo, Joseph L., Callister, Tracy, Phillips, Roland, Lippolis, Nicholas, Winterton, John, Meymandi, Sheba, Heilman, Karl, Oren, Ron, Zolty, Ronald, Brottman, Michael, Gunawardena, D.R., Adams, Kirkwood, Barnard, Denise, Klapholz, Marc, Fulmer, James, Maggioni AP, Greene SJ, Fonarow GC, Böhm M, Zannad F, Solomon SD, Lewis EF, Baschiera F, Hua TA, Gimpelewicz CR, Lesogor A, Gheorghiade M, Ramos S, Luna A, Miriuka S, Diez M, Perna E, Luquez H, Pinna JG, Castagnino J, Alvarenga P, Ibañez J, Blumberg ES, Dizeo C, Guerrero RA, Schygiel P, Milesi R, Sosa C, Hominal M, Marquez LL, Poy C, Hasbani E, Vico M, Fernandez A, Vita N, Vanhaecke J, De Keulenaer G, Striekwold H, Vervoort G, Vrolix M, Henry P, Dendale P, Smolders W, Marechal P, Vandekerckhove H, Oliveira M, Neuenschwande F, Reis G, Saraiva J, Bodanese L, Canesin M, Greco O, Bassan R, Marino RL, Giannetti N, Moe G, Sussex B, Sheppard R, Huynh T, Stewart R, Haddad H, Echeverria L, Quintero A, Torres A, Jaramillo M, Lopez M, Mendoza F, Florez N, Cotes C, Garcia M, Belohlavek J, Hradec J, Peterka M, Gregor P, Monhart Z, Jansky P, Kettner J, Reichert P, Spinar J, Brabec T, Hutyra M, Solar M, Pietilä M, Nyman K, Pajari R, Cohen A, Galinier M, Gosse P, Livarek B, Neuder Y, Jourdain P, Picard F, Isnard R, Hoppe U, Kaeaeb S, Rosocha S, Prondzinsky R, Felix S, Duengen HD, Figulla HR, Fischer S, Behrens S, Stawowy P, Kruells-Muench J, Knebel F, Nienaber C, Werner D, Aron W, Remppis B, Hambrecht R, Kisters K, Werner N, Hoffmann S, Rossol S, Geiss E, Graf K, Hamann F, von Scheidt W, Schwinger R, Tebbe U, Costard-Jaeckle A, Lueders S, Heitzer T, Leutermann-Oei ML, Braun-Dullaeus R, Roehnisch JU, Muth G, Goette A, Rotter A, Ebelt H, Olbrich HG, Mitrovic V, Hengstenberg C, Schellong S, Zamolyi K, Vertes A, Matoltsy A, Palinkas A, Herczeg B, Apro D, Lupkovics G, Tomcsanyi J, Toth K, Mathur A, Banker D, Bharani A, Arneja J, Khan A, Gadkari M, Hiremath J, Patki N, Kumbla M, Santosh MJ, Ravikishore AG, Abhaichand R, Maniyal V, Nanjappa M, Reddy PN, Chockalingam K, Premchand R, Mahajan V, Lewis B, Wexler D, Shochat M, Keren A, Omary M, Katz A, Marmor A, Lembo G, Di Somma S, Boccanelli A, Barbiero M, Pajes G, De Servi S, Greco DC, De Santis F, Floresta A, Visconti LO, Piovaccari G, Cavallini C, Di Biase M, Masini DF, Vassanelli C, Viecca M, Cangemi DF, Pirelli S, Borghi C, Volpe M, Branzi A, Percoco DG, Severi S, Santini A, De Lorenzi E, Metra M, Zacà V, Mortara A, Tranquilino FP, Babilonia NA, Ferrolino AM, Manlutac B, Dluzniewski M, Dzielinska Z, Nowalany-Kozie E, Mazurek W, Wierzchowiecki J, Wysokinski A, Szachniewicz J, Romanowski W, Krauze-Wielicka M, Jankowski P, Berkowski P, Szelemej R, Kleinrok A, Kornacewicz-Jac Z, Vintila M, Vladoianu M, Militaru C, Dan G, Dorobantu M, Dragulescu S, Kostenko V, Vishnevsky A, Goloschekin B, Tyrenko V, Gordienko A, Kislyak O, Martsevich S, Kuchmin A, Karpov Y, Fomin I, Shvarts Y, Orlikova O, Ershova O, Berkovich O, Sitnikova M, Pakhomova I, Boldueva S, Tyurina T, Simanenkov V, Boyarkin M, Novikova N, Tereschenko S, Zadionchenko V, Shogenov Z, Gordeev I, Moiseev V, Wong R, Ong HY, Le Tan J, Goncalvesova E, Kovar F, Skalina I, Kasperova V, Hojerova S, Szentivanyi M, Stancak B, Babcak M, Kycina P, Poliacik P, Toth P, Sirotiakova J, Lopez de Sa E, Bueno MG, Selles MM, Cabrera JA, Freire RB, Gonzalez Juanatey JR, Comin J, Soriano F, Lopez A, Vicho R, Lama MG, Schaufelberger M, Brunotte R, Ullman B, Hagerman I, Cizinsky S, Cherng WJ, Yu WC, Kuo CT, Chang KC, Lai WT, Kuo JY, Ural D, Badak O, Akin M, Yigit Z, Yokusoglu M, Yilmaz M, Abaci A, Ebinc H, Perlman R, Parish D, Bergin J, Burnham K, Brown C, Lundbye J, Williams C, Eisen H, Juneman E, Joseph S, Peberdy MA, Peura J, Gupta V, Habet K, French W, Mody F, Graham S, Hazelrigg M, Chung E, Dunlap S, Nikolaidis L, Najjar S, Katz R, Murali S, Izzo JL, Callister T, Phillips R, Lippolis N, Winterton J, Meymandi S, Heilman K, Oren R, Zolty R, Brottman M, Gunawardena DR, Adams K, Barnard D, Klapholz M, and Fulmer J

Subjects
Male, medicine.medical_specialty, Cardiotonic Agents, ASTRONAUT, Diabetic Cardiomyopathies, Administration, Oral, Kaplan-Meier Estimate, Placebo, Diabete, chemistry.chemical_compound, Double-Blind Method, Fumarates, Internal medicine, Diabetes mellitus, Troponin I, Renin, Clinical endpoint, medicine, Humans, Prospective Studies, Heart Failure, Ejection fraction, business.industry, Surrogate endpoint, Aliskiren, Middle Aged, medicine.disease, Amides, Hospitalization, Endocrinology, Death, Sudden, Cardiac, Treatment Outcome, chemistry, Heart failure, Female, Cardiology and Cardiovascular Medicine, business, aliskiren
Abstract

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether alis- kiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post- discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B- type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P ¼ 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P ¼ 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P , 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldoster- one relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P ¼ 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.

Published
2013

5. Charakterizace TRAILem indukované, receptor-specifické signalizace v nádorových buňkách

Author

Peterka, Martin, Anděra, Ladislav, and Rohlena, Jakub

Subjects
apoptóza, apoptosis, signalizace, death receptors, receptory smrti, TRAIL, signaling
Abstract

TNF-related apoptosis-inducing ligand (TRAIL) is a member of TNF family expressed mainly by hematopoietic cells. TRAIL brought significant attention mainly for its ability to trigger apoptosis in a number of cancer cells. In addition to apoptosis, TRAIL can induce several other signaling pathways such as activation of MAP kinases or canonical NF-B signaling. Human TRAIL can bind to five receptors but only two of them (death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5) can trigger TRAIL-mediated apoptotic and non-apoptotic signaling in target cells. Both receptors are ubiquitously expressed on normal and cancer cells, but the relative contribution of DR4 and DR5 to TRAIL-induced signaling is not well known. Using DR4/DR5-specific variants of TRAIL, we examined how individual receptor contributes to the induction of apoptosis and NF-B, JNK, p38, ERK1/2 and TAK1 signaling pathways in selected colorectal cells. We found that in DLD-1 cells, apoptosis and activation of JNKs are mainly mediated by DR4-selective ligand. In TRAIL-resistant HT-29 cells, we show that though DISC formation and activation of caspase-8 proceeds mainly via DR4-specific signaling, activation of NF-B pathway is mainly triggered by DR5 selective ligand. In other cells and analyzed signaling pathways both receptor-specific ligands triggered very...

Published
2013

6. Marketing communication of FIBA World Championship for Women 2010

Author

Peterka, Martin, Šíma, Jan, and Blažek, Daniel

Subjects
basketball, SWOT analýza, marketingová komunikace, marketing communication, SWOT analysis, basketbal
Abstract

Title: Marketing Communication of FIBA Women Basketball Championship 2010 Goal: The goal of my thesis is to describe marketing communication during the World Women Championship 2010 on the basis of observation and my own activity. The thesis should be able to describe different parts of marketing communication during the sport event. The goal is to create the instruction for one of possibilities, how to form marketing communication of a sport event with the help of the establishment description and the existence of marketing communication. Methods: The main method is descriptive analysis. The work uses evaluation proposal and demonstration, as well. SWOT analysis is made of found data. Results: The theses proved that all parts of marketing communication should be mutually connected and consider each other. It deals mainly with Public Relations which focus first of all on reaching needed popularity. Specialised and mass media are used. Information flow from a sport organisation to media representants should keep the balance between the quality and the quantity. Key words: marketing communication, basketball, SWOT analysis.

Published
2011

7. Activation and function of BH3-only proteins from the Bcl-2 family

Author

Peterka, Martin, Anděra, Ladislav, and Pavlů, Barbora

Subjects
biological phenomena, cell phenomena, and immunity
Abstract

The Bcl-2 (B-cell lymphoma-2) family of proteins comprises crucial regulators of apoptosis in metazoans. In mammals, Bcl-2 family members regulate mitochondrial outer membrane permeabilization (MOMP), which leads to the release of pro-apoptotic molecules from the mitochondrial intermembrane space and subsequent apoptosis. Defects in the Bcl-2 signaling can result in various pathological conditions including cancer. BH3-only proteins form a pro-apoptotic subset of the Bcl-2 family. They mainly act as sensors of various pro-apoptotic stimuli such as cytokine deprivation, genotoxic stress, activated "death receptors" and others. In mammals, over ten BH3-only proteins have been identified, eight of which have been linked to the regulation of MOMP. These "conventional" BH3-only proteins are Bim, Bid, Puma, Noxa, Bad, Hrk, Bik and Bmf. This thesis provides an overview of their origin, structure, activation and involvement in apoptosis.

Published
2011

9. The Current Financial Crisis and Its Impact on International Trade

Author

Peterka, Martin, Drozen, František, and Marková, Jana

Subjects
financial crisis, automotive industry, protekcionismus, mezinárodní obchod, kreditní deriváty, bankovnictví, automobilový průmysl, banking, finanční krize, international trade, credit derivatives, protectionism
Abstract

The thesis is aimed at explanation of the factors that led to the creation of the current financial crisis in their mutual context. Emphasis is placed on the way of providing mortgages in the USA, policy of FED and credit derivatives. The impacts of the crisis on banking, stock and commodity markets, building industry and automotive industry are discussed as important determinants of international trade. It is shortly mentioned how countries like Germany, China or Czech Republic dealt with the crisis. The final part of the thesis is devoted to the impacts of the crisis on international trade, these impacts result from the issues that are described in the first two parts. Discussed are the commodity and territorial structures of the international trade during the years of crisis. Also the impacts on the foreign trade of the Czech Republic are stressed.

Published
2009

10. Investments into the precious metals and stones

Author

Peterka, Martin, Drozen, František, and Drozenová, Alice

Abstract

Práce se zaměřuje na oblast drahých kovů a kamenů z hlediska jejich využití k investičním účelům. Zabývá se základními charakteristikami jednotlivých druhů drahých kovů a kamenů, způsoby jejich využití v hospodářství, strukturou trhu s nimi, vývojem ceny s důrazem na hlavní cenové výkyvy, jejich příčiny a důsledky. Dále jsou zmíněny oblasti jejich těžby a společnosti těžbu provádějící. Největší část práce je věnována investičním instrumentům spojeným s drahými kovy a kameny, trhům, na nichž jsou obchodovány, a jejich dostupnosti a vhodnosti pro drobné investory.

Published
2008

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